Abstract

Here we report a robust G‐quadruplex (G4) dimer‐guided transmembrane DNA nanovehicle for targeted payload delivery, based on dimeric G4‐proximized aptamers that efficiently target transferrin receptors (TfR) over‐expressed on cancer cell surface. A monomolecular G4 (mono‐G4) named 93del that stably forms the interlocked dimeric structure is employed as the controlling module, which responds to environmental K+ and thereby holds two TfR aptamers at the proximity state. It endows the designed DNA system with over 3‐fold enhancement in cellular internalization, enabling the cancer‐specific delivery of fluorescent G4 ligands and therapeutic drugs for cellular imaging and treatment.

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